In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Animals and Treatments
2.3. Total RNA Extraction and Real-Time PCR Quantification
Target | Accession Number | Forward Primer | Reverse Primer |
---|---|---|---|
Cyp2a4 | NM_009997 | GGAAGACGAACGGTGCTTTC | CCCGAAGACGATTGAGCTAATG |
Cyp3a11 | NM_007818 | CGCCTCTCCTTGCTGTCACA | CTTTGCCTTCTGCCTCAAGT |
Cyp2c37 | NM_010001 | ATACTCTATATTTGGGCAGG | GTTCCTCCACAAGGCAAC |
Cyp2c39 | NM_010003 | GGAGACAGAGCTGTGGC | TAAAAACAATGCCAAGGCCG |
Cyp2d22 | NM_019823 | GGGCCTTTGTTACCATGTTGG | TACTCGGCGCTGCACATCTG |
β-actin | NM_007393 | TGTTACCAACTGGGACGACA | GGGGTGTTGAAGGTCTCAAA |
2.4. Liver Microsome Preparation and Determination of Cyp Activity
2.5. Inhibitory Effects of GA on Cytochrome P450s
2.6. Enzymatic Kinetic Study of Inhibition
2.7. cDNA-Expressed CYP3A4 Inactivation Assay
2.8. Statistical Analysis
3. Results
3.1. Inhibition of CYP450 Activity by GA in HLMs
3.2. Mechanism-Based Inhibition of CYP3A4 by GA
3.3. Inhibition of Recombinant CYP3A4 by GA
3.4. Inhibition of CYPs by GA in Mice
3.5. Effects of GA on the mRNA Expression Levels of CYPs
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Lv, Q.-L.; Wang, G.-H.; Chen, S.-H.; Hu, L.; Zhang, X.; Ying, G.; Qin, C.-Z.; Zhou, H.-H. In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4. Int. J. Environ. Res. Public Health 2016, 13, 84. https://doi.org/10.3390/ijerph13010084
Lv Q-L, Wang G-H, Chen S-H, Hu L, Zhang X, Ying G, Qin C-Z, Zhou H-H. In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4. International Journal of Environmental Research and Public Health. 2016; 13(1):84. https://doi.org/10.3390/ijerph13010084
Chicago/Turabian StyleLv, Qiao-Li, Gui-Hua Wang, Shu-Hui Chen, Lei Hu, Xue Zhang, Guo Ying, Chong-Zhen Qin, and Hong-Hao Zhou. 2016. "In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4" International Journal of Environmental Research and Public Health 13, no. 1: 84. https://doi.org/10.3390/ijerph13010084